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The paper deals with the torques of external muscles acting on the upper ankle joint under weight-bearing conditions and their importance in diagnosing and treating the human foot. Experimental data were collected and calculations were performed. Based on the experiments with the biomechanical model of the foot and upper ankle joint, it was shown how the changes in the force arms of the external muscles of the foot under weight-bearing conditions, change the torque. The real values of muscle forces and torques of the external muscles of the foot were calculated. Taking into account the distance of the lines of muscle action from the axis of rotation of the upper ankle joint the rotational force of the muscles was calculated. The influence of changing the force arm on the rotational efficiency of the muscle balancing the moment of gravity was shown. Knowledge of muscle torque under weight-bearing conditions is crucial for correctly assessing foot biomechanics. It has been shown that torque (gravitational and muscular), not pure force, is crucial when assessing the rotational capacity of the analyzed joint. A change in the approach to diagnostics and treating paresis or weakness of extrinsic foot muscles was proposed through the manipulation of the distance of their action line from the axis of joint rotation., (© 2024. The Author(s).)

The subject of the paper is a review of multidimensional data analysis methods, which is the canonical analysis with its various variants and its use in omics data research. The dynamic development of high-throughput methods, and with them the availability of large and constantly growing data resources, forces the development of new analytical approaches that allow the review of the analyzed processes, taking into account data from various levels of the organization of living organisms. The multidimensional perspective allows for the assessment of the analyzed phenomenon in a more realistic way, as it generally takes into account much more data (including OMICs data). Without omitting the complexity of an organism, the method simplifies the multidimensional view, finally giving the result so that the researcher can draw practical conclusions. This is particularly important in medical sciences, where the study of pathological processes is usually aimed at developing treatment regimens. One of the primary methods for studying biomedical processes in a multidimensional approach is the canonical correlation analysis (CCA) with various variants. The use of CCA unique methodologies for simultaneous analysis of multiset biomolecular data opens up new avenues for studying previously undiscovered processes and interdependencies such as e.g. in the tumor microenvironment (TME) connected to intercellular communication. Because of the huge and still untapped potential of canonical correlation, in this review available implementations of CCA techniques are presented. In particular, the possibility of using the technique of canonical correlation analysis for OMICs data is emphasized., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Monika Piwowar reports article publishing charges was provided by Jagiellonian University in Kraków Medical College., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hyperandrogenism is among the most common endocrine disorders in women. Clinically, it manifests as hirsutism, acne, and alopecia. A healthy lifestyle, including nutritious dietary patterns and physical activity, may influence the clinical manifestation of the disease. This study determined the effect of a low-glycemic index anti-inflammatory diet on testosterone levels and sex hormone-binding globulin (SHBG) and clinical symptoms in hyperandrogenic women at their reproductive age., Methods: The study included 44 overweight and obese women diagnosed with hyperandrogenism. The anthropometrics (weight, height, body mass index, waist circumference, hip circumference), physical activity, and dietary habits were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was <0.001. Serum testosterone and SHBG levels were measured using automated immunoassay instruments., Results: The intervention based on a low-glycemic index diet with anti-inflammatory elements and slight energy deficit decreased total testosterone levels (p<0.003), increased SHBG levels (p<0.001), and decreased the free androgen index (FAI; p<0.001). Post-intervention, overall well-being was much higher than in the pre-intervention period (p<0.001), and stress was diminished (p<0.001). Western nutritional patterns positively correlate with clinical hyperandrogenism progression, whereas several factors of the low-glycemic index diet with anti-inflammatory elements and slight energy deficit positively associate with reduced clinical hyperandrogenism symptoms., Conclusions: In overweight and obese women, proper selection of diet, introduction of moderate physical activity, and reduction in weight, stress factors, and alcohol consumption translate into several positive effects, including reduced FAI and symptoms such as acne, hirsutism, menstrual disorders, and infertility., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model ( Mus musculus SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity.

Background: The aim of this study was to investigate the role of urine-derived extracellular vesicles (uEVs) in diabetic kidney disease (DKD) in patients diagnosed with type 2 diabetes mellitus (T2DM)., Methods: UEVs were characterized by size distribution and microRNA content by next-generation small RNA sequencing and quantitative reverse transcription PCR., Results: A subset of sixteen miRNAs enriched in T2DM patients with DKD, including hsa-miR-514a-5p, hsa-miR‑451a, hsa-miR-126-3p, hsa-miR-214, or hsa-miR‑503 was identified. Eight miRNAs as hsa-miR-21-3p, hsa-miR-4792, hsa-miR‑375, hsa-miR-1268a, hsa-miR-501-5p, or hsa-miR-582 were downregulated. Prediction of potential target genes and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed possible functions related to cellular processes such as apoptosis, inflammation, and tissue remodeling, that promote diabetic complications, such as DKD. Among them, hsa-miR-375, hsa-miR-503, and hsa-miR-451a make important contribution. Additionally, downregulated hsa-miR-582-5p has not been reported so far in any diabetes-related pathways., Conclusions: This study revealed the most significant miRNAs in uEVs of patients with T2DM. However, as this is a bioinformatic prediction that we performed based on the putative targets of the identified miRNAs. Thus, further in vitro functional studies are needed to confirm our findings. Knowing the fact that EVs are crucial in transferring miRNAs, there is a great need toto discover their involvement in the pathomechanism of T2DM-related kidney disease., (© 2023. The Author(s).)

Purpose: The aim of this paper was the application of a new dynamic-passive method of treatment in correction of hallux valgus and coexisting static deformities of the foot (transverse-plane and plano-valgus foot)., Methods: The study involved 50 patients; 26 with full big toe correction after the passive correction grip (group I) and 24 with big toe correction requiring additional passive abduction (group II). The patients regularly performed exercises using the designed device according to the planned schedule. The progress of the correction was assessed by a medical examination and additional tests., Results: The cross-sectional area [cm2 ] of the abductor hallucis muscle in three-time points among I and II groups of patients with the hallux valgus was measured based on MRI images. The STIR examination showed, among others, the abductor hallucis muscle edema after exercises with the DPc device were carried out. It evidences that exercises with the new device activate the muscle. Alignment of the big toes of both feet in groups I and II were obtained with a statistically significant result ( p < 0.05). The percentage progression of correction for HV and I/II IM was calculated., Conclusions: Based on the new correction approach the alignment of the big toe phalanges and the remaining toes was obtained. The passive setup of the tendons with their distal inserts at the level of the big toe phalanges to the correct path of their course with the withdrawal of articular subluxations was obtained. Simultaneously, the big toe's passive correction was dynamically consolidated through a specially selected set of exercises.

(1) Background: Static foot deformities, including hallux valgus, are common deformities. The subject under consideration is the role of extrinsic and intrinsic muscles working within muscular systems that shape the arches of the foot and the alignment of the toes. (2) Methods: Based on a literature review, the muscle systems were analyzed. The systems under consideration were as follows: "tendon stirrup" (system I); muscles complementary to the tendon stirrup (system II); "foot lever" (system III); muscles complementary to system III (system IV); "reins of hallux" (system V), a muscular system having distal inserts on the hallux. The shape of the foot arches was analyzed in this context. (3) Results: The correct arch architecture of the foot stabilized mainly by the extrinsic muscle systems determining the function of the intrinsic muscle systems of the foot is described. The proper function of muscular systems shaping the arches of the foot is a prerequisite for the proper function of muscles directly responsible for the alignment of the big toe (hallux) and other foot toes. (4) Conclusion: The action of muscles should be considered in groups (systems) because the action of the group of muscles results in the creation of a new quality of movement. The analysis of individual muscle-pulling forces, especially the moments of force in the weight-bearing foot, may lead to extremely incorrect conclusions. In pathological cases, the restoration of the correct arches of the foot guarantees the recovery of the correct function of the pulling forces of the foot muscles responsible for the physiological alignment of the hallux. This is especially important concerning conservative and surgical treatment of hallux valgus.

This study aimed to investigate the association between selected variants of genes related to dopamine metabolism pathways and the risk of and progression of Parkinson's disease (PD). This prospective cohort study was conducted in one academic teaching hospital. The study was conducted on 126 patients diagnosed with idiopathic Parkinson's disease. Blood samples were collected to conduct a genotyping of MAOB, DRD1, DRD2, and DDC genes. Genotype and allele frequencies of MAOB (rs1799836) variants were not associated with the course of PD. Genotype and allele frequencies of DRD2 (rs2283265) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DRD2 (rs1076560) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DDC (rs921451) variants were not associated with the course of PD., (© 2022. The Author(s).)

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson's disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls. This study compared the oral microbiota composition of 59 patients with PD and 108 healthy controls (without neurodegeneration) using 16S rRNA gene amplicon sequencing. According to results, oral microbiota in patients with PD is different compared from healthy controls. In particular, decreased abundance of Proteobacteria, Pastescibacteria, and Tenercutes was observed. The oral cavity of patients with PD was characterized by the high relative abundance of bacteria from the genera Prevotella , Streptococcus , and Lactobaccillus. There were also differences in food preferences between patients with PD and healthy controls, which revealed significantly higher intake of margarine, fish, red meat, cereals products, avocado, and olives in the patients with PD relative to healthy controls. Strong positive and negative correlations between specific food products and microbial taxa were identified.

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the Lactobacillus bacterial population, which contributes to the fortification of the intestinal barrier and inhibits the translocation phenomenon. The acquired knowledge can be used to limit the development of sepsis in newborns in hospital neonatal intensive care units.

(1) Background: The purpose of this study was to observe segmental phase angle (PhA) and body composition fluctuation of elite ski jumpers. (2) Methods: In the study, 12 professional ski jumpers took part. Body composition was estimated with segmental multi-frequency bioelectrical impedance analysis. Repeated ANOVA was used to check the parameters' variability in time. The symmetry between the right and left side of the body was verified with the t -test for dependent samples. Pearson's linear correlation coefficient was calculated. (3) Results: The most stable parameter was body weight. An increase in the visceral fat area was noted, the fat-free mass dropped, and significant changes were noted in the internal and external cell water parameters. Parameters connected with water between the right and left side of the body were symmetrical. Significant correlation between PhA values and body parameters with regard to fat tissue and PhA values of the legs was noticed when PhA was measured at 50 kHz. (4) Conclusions: PhA could be considered as a ski jumper body symmetry monitoring tool. The described relationship may be useful for the assessment of body fat change, which, in the case of jumpers, is crucial. Moreover, our data suggest that segmental PhA evaluation could be a good solution for ski jumpers as a confirmation if lowered body mass and low BMI are still healthy and increase the chance for longer jumps and good performance.

The distribution of nucleotides spacing in human genome was investigated. An analysis of the frequency of occurrence in the human genome of different sequence lengths flanked by one type of nucleotide was carried out showing that the distribution has no self-similar (fractal) structure. The results nevertheless revealed several characteristic features: (i) the distribution for short-range spacing is quite similar to the purely stochastic sequences; (ii) the distribution for long-range spacing essentially deviates from the random sequence distribution, showing strong long-range correlations; (iii) the differences between (A, T) and (C, G) nucleotides are quite significant; (iv) the spacing distribution displays tiny oscillations.

A huge amount of atomized biological data collected in various databases and the need for a description of their relation by theoretical methods causes the development of data integration methods. The omics data analysis by integration of biological knowledge with mathematical procedures implemented in the OmicsON R library is presented in the paper. OmicsON is a tool for the integration of two sets of data: transcriptomics and metabolomics. In the workflow of the library, the functional grouping and statistical analysis are applied. Subgroups among the transcriptomic and metabolomics sets are created based on the biological knowledge stored in Reactome and String databases. It gives the possibility to analyze such sets of data by multivariate statistical procedures like Canonical Correlation Analysis (CCA) or Partial Least Squares (PLS). The integration of metabolomic and transcriptomic data based on the methodology contained in OmicsON helps to easily obtain information on the connection of data from two different sets. This information can significantly help in assessing the relationship between gene expression and metabolite concentrations, which in turn facilitates the biological interpretation of the analyzed process., Competing Interests: The authors have declared that no competing interests exist.

Analysis of large data sets is currently a major challenge. Strong efforts are being undertaken to tackle this problem by developing new methods or modifying existing ones. The Z association method is a new method for describing directional association in contingency tables. It allows to arbitrarily group categories for each of the two variables, for which the contingency table is analyzed. The Z coefficient was calculated on a sample data set with gene mutations in different cancer types. Results showed some association with both gene mutations and annotation groups. Detailed results obtained for particular cancer types versus particular genes and annotation groups were in line with well-known facts in cancer genomics. The "MEUSassociation" R library allows to analyze the directional association between two categorical variables, and the mutual relationship is summarized in a contingency table, by means of the Z association coefficient. The method implemented in the library allows to compute the standard Z coefficient and to apply it in a case, where all possible singular coefficients Z(A:B) are computed at the same time, giving information of association between particular rows and columns. Investigating the ranked list of the highest singular coefficients allows to reduce the complexity of a large-scale data set. Both the Z coefficient and its R implementation are important tools in categorical data analysis.

The association of FokI (rs2228570), a polymorphism of the vitamin D receptor gene, with intervertebral disc degeneration (IDD) has been investigated in a multitude of studies. However, conflicting results of these studies led to emergence of several meta-analyses over the past few years. Despite the increased statistical power, these meta-analyses have failed to provide uniform and conclusive data on the relationship of FokI with IDD. The aim of this study was to present a comprehensive review based on the most up-to-date meta-analyses on the association of FokI with IDD. A comprehensive search of all major databases was conducted to identify meta-analyses investigating relation between FokI and IDD. No date or language restrictions were applied. The Jadad decision algorithm was utilized to evaluate included meta-analyses and identify the one providing the best evidence. A total of 7 meta-analyses (n = 2580 original patients), that included six to ten case control studies, analyzed the association of FokI polymorphism with IDD. The meta-analysis of the highest quality supported the notion that overall there is no statistically significant association between FokI polymorphism and IDD. However, the authors showed that Caucasians have a reduced risk of IDD and Hispanics have an increased risk of IDD in the dominant and dominant/homozygous/heterozygous models of FokI polymorphism. While currently there is no evidence of an association between FokI polymorphism and IDD in the general population, ethnic predisposition has been shown., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim of the Study: One of the critical steps in molecular oncology diagnostics is obtaining high quality genomic DNA. Therefore, it is important to evaluate and compare the techniques used to extract DNA from tissue samples. Since formalin-fixed, paraffin-embedded (FFPE) tissues are routinely used for both retrospective and prospective studies, we compared three commercially available methods of nucleic acid extraction in terms of quantity and quality of isolated DNA., Material and Methods: Slides prepared from 42 FFPE blocks were macro-dissected. Resulting material was divided and processed simultaneously using three extraction kits: QIAamp DNA FFPE Tissue Kit (QIAGEN), Cobas DNA Sample Preparation Kit (Roche Molecular Systems) and Maxwell 16 FFPE Plus LEV DNA Purification Kit (Promega). Subsequently, quantity and quality of obtained DNA samples were analysed spectrophotometrically (NanoDrop 2000, Thermo Scientific). Results of quantitative analysis were confirmed by a fluorometric procedure (Qubit 3.0 Fluorometer, Life Technologies)., Results: The results demonstrated that the yields of total DNA extracted using either Maxwell or Cobas methods were significantly higher compared to the QIAamp method ( p < 0.001). The Maxwell Extraction Kit delivered DNA samples of the highest quality ( p < 0.01). However, the highest total yield of extracted DNA was achieved with the Cobas technique, which may be due to a higher volume of eluate compared to the Maxwell method., Conclusions: To our knowledge, this is the first paper which directly compares three extraction methods: Cobas, Maxwell and QIAamp. The data herein provide information required for the selection of a protocol that best suits the needs of the overall study design in terms of the quantity and quality of the extracted DNA., Competing Interests: The authors declare no conflict of interest.

Background/aim: Most melanomas develop in hypoxic conditions. Since hypoxia via HIF-1 induces glycolysis, a process essential for malignant melanoma growth/survival, the goal of this study was to analyze the influence of hypoxia on the expression of HIF-1 target genes involved in glucose metabolism., Materials and Methods: The response of melanoma cell lines to hypoxic conditions was analyzed by RT-PCR and western blotting. A Kaplan-Meier survival analysis for patients with high and low expression level of PFKFB4 was performed. Further analysis of patients' data was performed using the R/Bioconductor environment., Results: Induction of PFKFB4 gene expression can be considered a crucial mechanism behind glycolysis enhancement in hypoxic melanoma cells. Analysis of a publicly available database revealed that high PFKFB4 expression contributes to poor prognosis of melanoma patients., Conclusion: Currently available anti-melanoma therapeutic strategies may significantly benefit from agents targeting PFKFB4 activity., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rationale: X-linked adrenoleukodystrophy (X-ALD) is a rare disorder caused by mutations in the ABCD1 gene, coding for peroxisomal membrane transporter adrenoleukodystrophy (ALD) protein. The disease is characterized by accumulation of very long chain fatty acids (VLCFAs) in tissues. Adult adrenomyeloneuropathy (AMN) and the cerebral inflammatory form of ALD are the main phenotypes presenting various symptoms., Patient Concerns: We report a case of 37-year-old patient with diagnosis of X-ALD, confirmed based on elevated VLCFA concentrations and genetic testing of ABCD1 gene. The complete clinical picture in the patient indicates AMN phenotype with cerebral involvement., Diagnoses: The reduced synthesis of unconjugated cholic and chenodeoxycholic acids, and the reduction to 28% to 29% of peroxisomal beta-oxidation of behenic acid and normal peroxisomal metabolism of pristanic and palmitic acid were observed in the X-ALD patient. Sanger sequencing of major genes involved in primary bile acid (BA) synthesis failed to identify pathogenic mutations of the investigated set of genes., Interventions: Plasma concentrations of BAs, VLCFAs, and beta-oxidation of C22:0, C16:0, and pristanic acid were studied in primary skin fibroblasts of the patient. In addition, we performed sequencing of the ABCD1, ABCD3, CYP7A1, CYP7B1, CYP27A1, HSD3B7, AKR1D1, and SLC27A5 genes in the X-ALD family., Outcomes: In the Polish family affected with AMN a dysregulation of the primary BA synthesis pathway was found., Lessons: We have demonstrated the coincidence of the adult form of X-ALD with abnormalities in BA synthesis. We suggest that decreased synthesis of BAs may be an additional dysfunction as a consequence of the ABCD1 c.659T>C, p.(Leu220Pro) mutation and may be further evidence that disturbed cholesterol metabolism is important in the pathology of ALD.

The paper presents the application of Grade Correspondence Analysis (GCA) and Grade Correspondence Cluster Analysis (GCCA) for ordering and grouping -omics datasets, using transcriptomic data as an example. Based on gene expression data describing 256 patients with Multiple Myeloma it was shown that the GCA method could be used to find regularities in the analyzed collections and to create characteristic gene expression profiles for individual groups of patients. GCA iteratively permutes rows and columns to maximize the tau-Kendall or rho-Spearman coefficients, which makes it possible to arrange rows and columns in such a way that the most similar ones remain in each other's neighbourhood. In this way, the GCA algorithm highlights regularities in the data matrix. The ranked data can then be grouped using the GCCA method, and after that aggregated in clusters, providing a representation that is easier to analyze-especially in the case of large sets of gene expression profiles. Regularization of transcriptomic data, which is presented in this manuscript, has enabled division of the data set into column clusters (representing genes) and row clusters (representing patients). Subsequently, rows were aggregated (based on medians) to visualise the gene expression profiles for patients with Multiple Myeloma in each collection. The presented analysis became the starting point for characterisation of differentiated genes and biochemical processes in which they are involved. GCA analysis may provide an alternative analytical method to support differentiation and analysis of gene expression profiles characterising individual groups of patients., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The study investigates measurable effects of cabbage leaf wraps on post-traumatic knee injury exudate absorption in men., Design: Case-control experiment on the same group of patients (before and after treatment)., Settings/location: One academic center and two hospitals., Subjects: The study was carried out on a group of patients with different degrees of injury severity in the acute stage of the knee injury who were divided into three groups based on the width of suprapatellar recess gap (3-5 mm in group 1, 6-10 mm in group 2, and 11 mm or more in group 3) as assessed by ultrasonography., Interventions: Each group of patients was divided into two subgroups, one of which comprised patients whose knees were treated with wraps containing cabbage leaves with ice (cases) and the others comprised patients treated with wraps without cabbage leaves, with cooling dressing only (controls)., Results: Significant progression in knee fluid uptake was observed in the acute stage of the knee injuries treated with cabbage wraps compared with control groups (p < 0.05). It was shown that the time, type of wraps, and a degree of severity of post-traumatic exudative knee inflammation affect the process of knee recovery (Friedman test for repeated measures p < 0.05). The most significant results were observed within first 24 h after the injury. Further decrease in the width of the recess gap after 5 days was observed., Conclusions: Application of cabbage wraps with ice to the knee in men may promote a reduction of swelling (by accelerating absorption of knee exudates) if applied during the acute stage of the knee injury.

Objectives: Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment., Material and Methods: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer., Results: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor., Conclusions: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.

In recent years a wide range of studies have shown that G protein-coupled receptors modulate a variety of cell functions through the formation of dimers. For instance, there is growing evidence for the dimerization of bradykinin or dopamine receptors, both as homodimers and heterodimers. A discovery of direct interactions of angiotensin II receptors with bradykinin 2 receptor (B2R) or dopamine D2 (D2R) receptor has led to a hypothesis on a potential dimerization between two latter receptors. In this study, we have demonstrated a constitutive colocalization of receptors on the membranes of HEK293 cells transiently transfected with plasmid vectors encoding B2R and D2R, fused with fluorescent proteins. The receptor colocalization was significantly enhanced by specific agonists of B2R or D2R after 5min following the addition, whereas simultaneous stimulation with these agonists did not influence the B2R/D2R colocalization level. In addition, B2R-D2R heterodimerization was confirmed with FLIM-FRET technique. The most characteristic signaling pathways for B2R and D2R, dependent on intracellular Ca 2+ and cAMP concentration, respectively, were analyzed in cells presenting similar endogenous expression of B2R and D2R. Significant changes in receptors' signaling were observed after simultaneous stimulation with agonists, suggesting transformations in proteins' conformation after dimerization. The evidence of B2R-D2R dimerization may open new perspectives in the modulation of diverse cellular functions which depend on their activation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The presented analysis concerns the inter-domain and inter-protein interface in protein complexes. We propose extending the traditional understanding of the protein domain as a function of local compactness with an additional criterion which refers to the presence of a well-defined hydrophobic core. Interface areas in selected homodimers vary with respect to their contribution to share as well as individual (domain-specific) hydrophobic cores. The basic definition of a protein domain, i.e., a structural unit characterized by tighter packing than its immediate environment, is extended in order to acknowledge the role of a structured hydrophobic core, which includes the interface area. The hydrophobic properties of interfaces vary depending on the status of interacting domains-In this context we can distinguish: (1) Shared hydrophobic cores (spanning the whole dimer); (2) Individual hydrophobic cores present in each monomer irrespective of whether the dimer contains a shared core. Analysis of interfaces in dystrophin and utrophin indicates the presence of an additional quasi-domain with a prominent hydrophobic core, consisting of fragments contributed by both monomers. In addition, we have also attempted to determine the relationship between the type of interface (as categorized above) and the biological function of each complex. This analysis is entirely based on the fuzzy oil drop model., Competing Interests: Authors declare no conflict of interest.

The aim of the study was to evaluate the frequency of breakfast and other meal consumption by adolescents and to assess the relationship between the first and the last meal consumption and sex, body mass index (BMI), and middle school and high school students' education level. The study was conducted in 2013-2014 among 3009 students (1658 girls and 1351 boys) from middle s and high schools in Krakow and Silesia (Poland). The data was obtained from questionnaires that were analyzed with a logistic regression model for measurable and dichotomous variables. Breakfast consumers were seen to eat other meals (second breakfast, lunch, dessert, supper) significantly more often than breakfast skippers. The main meal consumption habits depend on sex and change as adolescents age. Being a girl and a high school student predisposed participants to skip breakfast and supper more often. The BMI of breakfast consumers does not differ significantly from the BMI of breakfast skippers, so BMI might thus not be a sufficient marker of breakfast consumption regularity and dietary habits in an adolescent group. The importance of regularly eaten meals, especially breakfast, together with adequate daily dietary energy intake are beneficial for physical and psychological development and cannot be overestimated in nutritional education and it is necessary to promote healthy eating behavior for well-being in later adult life.

Introduction: Regenerative medicine for the treatment of urinary incontinence has become a popular area of focus in the search for therapies for this disease. The paper focused on women's quality of life assessment who were subjected to transplantation of MDSC (autologous muscle derived stem cells) to the urethral sphincter., Methods: The procedure was conducted in 16 female patients who completed the observation stage. Assessment of quality of life before and after the treatment (two and four years post-operation) was conducted based on the validated I-QOL questionnaire (the Polish language version)., Results: The questionnaire study showed that autologous cell therapy significantly improves quality of life in female patients suffering from stress urinary incontinence (SUI). The total I-QOL score increased from 49 (SD ± 7.7) before therapy to 77 (SD ± 5.4) two years post-operation. Four years after the procedure, quality of life remained at a higher level than before therapy, although quality of life decreased by several points when compared with the results from the two-year follow-up - 63 (SD ± 7.2). Patients reported significantly less concern related to their ability to reach the toilet to avoid incontinence, improved sleep at night, a higher level of satisfaction with life, and more satisfaction with their sexual lives (p<0.05)., Conclusion: The MDSC injection procedure for SUI treatment has significant improved quality of life in the majority of our patients in 2 and 4 year follow-up.

Background: The study of interactions between molecules belonging to different biochemical families (such as lipids and nucleic acids) requires specialized data analysis methods. This article describes the DNA Microarray Integromics Analysis Platform, a unique web application that focuses on computational integration and analysis of "multi-omics" data. Our tool supports a range of complex analyses, including - among others - low- and high-level analyses of DNA microarray data, integrated analysis of transcriptomics and lipidomics data and the ability to infer miRNA-mRNA interactions., Results: We demonstrate the characteristics and benefits of the DNA Microarray Integromics Analysis Platform using two different test cases. The first test case involves the analysis of the nutrimouse dataset, which contains measurements of the expression of genes involved in nutritional problems and the concentrations of hepatic fatty acids. The second test case involves the analysis of miRNA-mRNA interactions in polysaccharide-stimulated human dermal fibroblasts infected with porcine endogenous retroviruses., Conclusions: The DNA Microarray Integromics Analysis Platform is a web-based graphical user interface for "multi-omics" data management and analysis. Its intuitive nature and wide range of available workflows make it an effective tool for molecular biology research. The platform is hosted at https://lifescience.plgrid.pl/.

To date, the massive quantity of data generated by high-throughput techniques has not yet met bioinformatics treatment required to make full use of it. This is partially due to a mismatch in experimental and analytical study design but primarily due to a lack of adequate analytical approaches. When integrating multiple data types e.g. transcriptomics and metabolomics, multidimensional statistical methods are currently the techniques of choice. Typical statistical approaches, such as canonical correlation analysis (CCA), that are applied to find associations between metabolites and genes are failing due to small numbers of observations (e.g. conditions, diet etc.) in comparison to data size (number of genes, metabolites). Modifications designed to cope with this issue are not ideal due to the need to add simulated data resulting in a lack of p-value computation or by pruning of variables hence losing potentially valid information. Instead, our approach makes use of verified or putative molecular interactions or functional association to guide analysis. The workflow includes dividing of data sets to reach the expected data structure, statistical analysis within groups and interpretation of results. By applying pathway and network analysis, data obtained by various platforms are grouped with moderate stringency to avoid functional bias. As a consequence CCA and other multivariate models can be applied to calculate robust statistics and provide easy to interpret associations between metabolites and genes to leverage understanding of metabolic response. Effective integration of lipidomics and transcriptomics is demonstrated on publically available murine nutrigenomics data sets. We are able to demonstrate that our approach improves detection of genes related to lipid metabolism, in comparison to applying statistics alone. This is measured by increased percentage of explained variance (95% vs. 75-80%) and by identifying new metabolite-gene associations related to lipid metabolism.

Aims: We evaluated the safety, feasibility and initial effects of therapy with muscle-derived cells (MDCs) for women with stress urinary incontinence (SUI)., Methods: MDCs were isolated from an upper-arm muscle biopsy from 16 women with SUI. Cells were isolated by enzymatic digestion and expanded in vitro for 8-10 weeks. A quantity of 0.6-25 × 10(6) of the obtained cells were injected transurethrally into the urethral rhabdosphincter of women under local anesthesia. The cells were placed circumferentially at the 9, 12, and 3 O'clock positions with endoscopic guidance., Results: The initial results of the treatment of SUI with adult muscle-derived stem cells demonstrate the safety and feasibility of using these cells. The 2-year follow-up revealed a 75% success rate, with some patients achieving complete improvement (50%) and some patients achieving partial improvement (25%), suggesting that the prospects for this method are encouraging., Conclusions: Stem cell therapy promises to become a minimally invasive method for the regeneration of the urethral rhabdosphincter muscle. Injecting a small number of cells does not preclude obtaining the desired therapeutic result., (© 2013 Wiley Periodicals, Inc.)

The "fuzzy oil drop" model assumes that the idealized hydrophobic core in a protein body can be described by a 3D Gauss function. The structure of the 1ICF protein (cathepsin), which participates in the proteolysis process and has cysteine-type peptidase activity, has been analyzed on the basis of the "fuzzy oil drop" model. The authors have determined the contribution of individual exon fragments to the creation of a common hydrophobic core and assessed the involvement of each chain in this process, depending on the number of complexed chains. Quantitative assessment of exons, chains, dimers, and the whole complex suggest that each of these units plays a different role in shaping the protein's hydrophobic core.

This paper discusses the structural role of fragments encoded by individual exons in proteins. Selected enzymes (hydrolases, transferases, ligases) reveal the presence of at least one exon fragment whose contribution to the protein's hydrophobic core is in line with theoretical expectations. This phenomenon is confirmed by quantitative analysis of the hydrophobicity density distribution in protein molecules. Results are compared with a 3D Gaussian function, treated as an "idealized" distribution of hydrophobicity density, with the highest values observed near the center of the molecule and near-zero values on its surface. At least one accordant exon fragment has been identified in each of the proteins subjected to analysis. On the basis of these results the authors propose that accordant exons are responsible for tertiary structural stabilization of proteins by ensuring the generation of a stable hydrophobic core., (© 2013 Published by Elsevier Ltd.)

Unlabelled: The web application oriented on identification and visualization of protein regions encoded by exons is presented. The Exon Visualiser can be used for visualisation on different levels of protein structure: at the primary (sequence) level and secondary structures level, as well as at the level of tertiary protein structure. The programme is suitable for processing data for all genes which have protein expressions deposited in the PDB database. The procedure steps implemented in the application: I) loading exons sequences and theirs coordinates from GenBank file as well as protein sequences: CDS from GenBank and aminoacid sequence from PDB II) consensus sequence creation (comparing amino acid sequences form PDB file with the CDS sequence from GenBank file) III) matching exon coordinates IV) visualisation in 2D and 3D protein structures. Presented web-tool among others provides the color-coded graphical display of protein sequences and chains in three dimensional protein structures which are correlated with the corresponding exons., Availability: http://149.156.12.53/ExonVisualiser/

The past few years brought high development in obtaining and culturing autologous adult stem cells. In this paper we review publications of experimental investigations and clinical trials of the muscle-derived cells and the application in the treatment of stress urinary incontinence among women. Mesenchymal stem cells (MSCs) can be obtained from bone marrow but it is associated with a painful biopsy procedure. Collection of muscle-derived stem cells (MDSCs) is less harmful because the skeletal muscle biopsy is performed with a small caliber needle in local anesthesia. The stem-based therapy could be the next step in the treatment of urinary incontinence. There are still many elements of therapy such as effectiveness or long-term side effects which need to be researched.

The three-dimensional structures of a set of 'never born proteins' (NBP, random amino acid sequence proteins with no significant homology with known proteins) were predicted using two methods: Rosetta and the one based on the 'fuzzy-oil-drop' (FOD) model. More than 3000 different random amino acid sequences have been generated, filtered against the non redundant protein sequence data base, to remove sequences with significant homology with known proteins, and subjected to three-dimensional structure prediction. Comparison between Rosetta and FOD predictions allowed to select the ten top (highest structural similarity) and the ten bottom (the lowest structural similarity) structures from the ranking list organized according to the RMS-D value. The selected structures were taken for detailed analysis to define the scale of structural accordance and discrepancy between the two methods. The structural similarity measurements revealed discrepancies between structures generated on the basis of the two methods. Their potential biological function appeared to be quite different as well. The ten bottom structures appeared to be 'unfoldable' for the FOD model. Some aspects of the general characteristics of the NBPs are also discussed. The calculations were performed on the EUChinaGRID grid platform to test the performance of this infrastructure for massive protein structure predictions.

The number of natural proteins although large is significantly smaller than the theoretical number of proteins that can be obtained combining the 20 natural amino acids, the so-called "never born proteins" (NBPs). The study of the structure and properties of these proteins allows to investigate the sources of the natural proteins being of unique characteristics or special properties. However the structural study of NPBs can also been intended as an ideal test for evaluating the efficiency of software packages for the ab initio protein structure prediction. In this research, 10.000 three-dimensional structures of proteins of completely random sequence generated according to ROSETTA and FOD model were compared. The results show the limits of these software packages, but at the same time indicate that in many cases there is a significant agreement between the prediction obtained.

Background: Experimental observations classify the protein-folding process as a multi-step event. The backbone conformation has been experimentally recognized as responsible for the early-stage structural forms of a polypeptide. The sequence-to-structure and structure-to-sequence relation is critical for predicting protein structure. A contingency table representing this relation for tetrapeptides in their early-stage is presented. Their correlation seems to be essential in protein-folding simulation., Material/methods: The polypeptide chains of all the proteins in the Protein Data Bank were transformed into their early-stage structural forms. The tetrapeptide was selected as the structural unit. Tetrapetide sequences and structures were expressed by letter codes. The transformation of a contingency table of any size (here: 160,000x2401) to a 2x2 table performed for each non-zero cell of the original table allowed calculation of the rho-coefficient measuring the strength of the relation., Results: High values of the rho-coefficient extracted sequences of strong structural determinability and structures of high sequence selectivity. The web-site program to calculate the rho-coefficient ranking list was constructed to enable applying this method to any problem of contingency table analysis., Conclusions: The results revealed sequence-to-structure (and vice versa) correlation in early-stage folding. Surprisingly, the irregular structural forms of loops and bends appeared to be highly determined. Comparison of these results with another method based on information entropy revealed high accordance. The method oriented on interpretation of a large contingency table seems very useful especially for large-scale microarray analysis, a very popular technique in the post-genomic era.

Characteristics of 64 possible tandem trinucleotide repeats (TSSR) from Homo sapiens (hs), Mus musculus (mm) and Rattus norvegicus (rn) genomes are presented. Comparative analysis of TSSR frequency depending on their repetitiveness and similarity of the TSSR length distributions is shown. Comparative analysis of TSSR sequence motifs and association between type of motif and its length (n) using rho-coefficient method (quantitatively measuring the association between variables in contingency tables) is presented. These analyses were carried out in the context of neurodegenerative diseases based on trinucleotide tandems. The length of these tandems and their relation to other TSSR is estimated. It was found that the higher repetitiveness (n) the lower frequency of trinucleotides tandems. Differences between genomes under consideration, especially in longer than n=9 TSSR were discussed. A significantly higher frequency off A- and T-rich tandems is observed in the human genome (as well as in human mRNA). This observation also applies to mm and rn, although lower abundant in proportion to human genomes was found. The origin of elongation (or shortening) of TSSR seems to be neither frequency nor length dependent. The results of TSSR analysis presented in this work suggest that neurodegenerative disease-related microsatellites do not differ versus the other except the lower frequency versus the other TSSR. CAG occurs with relatively high frequency in human mRNA, although there are other TSSR with higher frequency that do not cause comparable disease disorders. It suggests that the mechanism of TSSR instability is not the only origin of neurodegenerative diseases.